Abstract
Background: The cytochrome P450 drug metabolizing enzymes CYP2D6 and CYP2C19 are the major targets for pharmacogenomics (PGx) testing and determining for drug response. Clinical dosing guidelines for specific drug-gene interactions (DGI) are publicly available through PharmGKB. The aim of this register study was to map the use of drugs in Denmark for drugs having actionable dosing guidelines (AG) i.e., dosing recommendations different from standard dosing for CYP2D6 or CYP2C19 DGI in terms of consumption. Methods: The Danish Register of Medicinal Product Statistics was the source to retrieve consumption in Defined Daily Dose (DDD) i.e., the assumed average maintenance dose per day for a drug used for its main indication in adults and number of users (2017 data). Clinical dosing guidelines were available from the PharmGKB website. Results: Forty-nine drugs have guidelines corresponding to 14.5% of total sales in DDD. Twenty-eight drugs have AG corresponding to 375.2 million DDD. Pantoprazole, lansoprazole, omeprazole, clopidogrel, and metoprolol constituted fifty-eight percent of the consumption in DDD of drugs having AG. The consumption of antidepressant drugs, opioids, and antipsychotic drugs were 157.0 million DDD; with 441,850 users, 48.9 million DDD; with 427,765 users, and 23.7 million DDD; with 128,935 users, respectively. Age distributions of consumption of drugs and drug combinations, e.g., for sertraline redeemed either alone or in combination with metoprolol and tramadol, are presented. Conclusion: This exploratory register study clearly showed that a large fraction of the Danish population, especially the elderly, are exposed to drugs or drug combinations for which there exist AG related to PGx of CYP2D6 or CYP2C19.
Highlights
Cytochromes P450 (CYP450) drug metabolizing enzymes are the major enzymes in catalyzing the oxidative biotransformation of 70%–80% of all drugs in clinical use to either inactive metabolites or active substances [1,2]
The aim of this register study was to map the use of drugs in Denmark for drugs having actionable dosing guidelines (AG) i.e., dosing recommendations different from standard dosing for CYP2D6 or CYP2C19 drug-gene interactions (DGI) in terms of consumption
Age distributions of consumption of drugs and drug combinations, e.g., for sertraline redeemed either alone or in combination with metoprolol and tramadol, are presented. This exploratory register study clearly showed that a large fraction of the Danish population, especially the elderly, are exposed to drugs or drug combinations for which there exist AG related to PGx of
Summary
Cytochromes P450 (CYP450) drug metabolizing enzymes are the major enzymes in catalyzing the oxidative biotransformation of 70%–80% of all drugs in clinical use to either inactive metabolites or active substances [1,2]. Consortium (CPIC) [6] and the Dutch Pharmacogenetics Working Group (DPWG) [7,8] both provide widely recognized clinical dosing guidelines for specific drug-gene interactions (DGI) [9,10]. These are compiled and publically available through the Pharmacogenomics Knowledgebase (PharmGKB; https://www.pharmgkb.org) [11]. The term phenoconversion introduces a complicating factor, which potentially can give rise to “genotype-phenotype” mismatches; a person scored as an EM or RM can be phenoconverted to a PM by co-medications [15] (drug–drug interactions) This means that the “true” number of PMs could be significantly higher compared to the number of PMs measured by PGx-testing alone. This study present data retrieved from The Danish Register of Medicinal Product Statistics [26]
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